MHC-I molecules expose the intracellular protein content on the cell surface, allowing T cells to detect foreign or mutated peptides. The combination of six MHC-I alleles each individual carries defines the sub-peptidome that can be effectively presented. We applied this concept to human cancer, hypothesizing that oncogenic mutations could arise in gaps in personal MHC-I presentation. To validate this hypothesis, we developed and applied a residue-centric patient presentation score to 9,176 cancer patients across 1,018 recurrent oncogenic mutations. We found that patient MHC-I genotype-based scores could predict which mutations were more likely to emerge in their tumor. Accordingly, poor presentation of a mutation across patients was correlated with higher frequency among tumors. These results support that MHC-I genotype-restricted immunoediting during tumor formation shapes the landscape of oncogenic mutations observed in clinically diagnosed tumors and paves the way for predicting personal cancer susceptibilities from knowledge of MHC-I genotype.

中文翻译：

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MHC-1基因型限制了致癌突变景观。

MHC-1分子暴露细胞表面上的细胞内蛋白质含量，从而使T细胞能够检测外源或突变的肽。每个个体携带的六个MHC-1等位基因的组合定义了可以有效表达的亚肽组。我们将这一概念应用于人类癌症，假设在个人MHC-I表现的缺口中可能出现致癌突变。为了验证该假设，我们开发了以残基为中心的患者表现评分并将其应用于1018例复发致癌突变中的9176例癌症患者。我们发现，基于患者MHC-1基因型的评分可以预测哪些突变更可能出现在其肿瘤中。因此，患者间突变的不良表现与肿瘤之间较高的发生频率相关。